tbuckley/cabot-search huggingface dataset:
Importance of <i>DICER1 </i>pathogenic variants in non-small cell lung cancer.
Authors: Samuel Wu, Mark Gordon Evans, Anne-Laure Chong, Paul Thorner, Pierre-Olivier Fiset, Yasmeen M. Butt, Matthew James Oberley, Zoran Gatalica, William D. Foulkes
Journal: Journal of Clinical Oncology (2023)

e20602 Background: DICER1 encodes a miRNA processing enzyme involved in regulation of cell proliferation and differentiation. The role of DICER1 pathogenic variants (PVs) in non-small cell lung cancer (NSCLC) is relatively unknown. Germline and/or somatic PVs have been reported in pleuropulmonary blastoma, pulmonary blastoma (PB), and low-grade/well-differentiated fetal adenocarcinoma (WDFLAC), with clustering of somatic PVs at specific metal ion binding residues referred to as hotspot alterations. PVs in CTNNB1, resulting in constitutive activation of the WNT signaling pathway, have also been implicated in PB and WDFLAC. This study seeks to establish the frequency of somatic DICER1 hotspot PVs that occur in all NSCLCs, their co-occurrence with other PVs in DICER1 and with alterations of CTNNB1/WNT signaling, and their histologic correlates. Methods: Molecular sequencing data collected from 12,146 NSCLCs at Caris Life Sciences were queried for cases featuring somatic DICER1 variants. For those tumors harboring hotspot PVs, sequencing for CTNNB1 and APC mutations was performed, as well as histological review, including examination of beta-catenin immunohistochemical (IHC) staining. Results: Of the 12,146 NSCLCs analyzed, 235 (1.9%) were found to have one or more DICER1 PVs. Of these 235, 225 cases demonstrated one variant, while 10 tumors featured two. Gene analysis revealed that 8 of the observed PVs cases contained hotspot alterations: 2 in the single variant cases and 6 in the double variant cases. The remaining 4 double variant cases harbored a combination of truncating, non-hotspot missense, or splice variants. No significant differences were observed for age or smoking status between DICER1 hotspot-positive and hotspot-negative groups. All but one tumor were considered to be in histologic spectrum of PB/WDFLAC. Of the 8 DICER1 hotspot-positive cases, 1 had a PV in APC, 4 had a CTNNB1 PV, 1 had a PV in both APC and CTNNB1, and 2 had neither. Beta-catenin IHC showed nuclear positivity in 5 tumors that had a PV in either CTNNB1 and/or APC.. Conclusions: This study demonstrates that DICER1 somatic hotspots select for morphologic features of tumor types such as PB and WDFLAC, but are not implicated in the most common forms of NSCLC. Furthermore, DICER1 hotspot-positive NSCLCs frequently harbor CTNNB1 and/or APC alterations, with many cases exhibiting nuclear staining by beta-catenin IHC, suggesting a possible synergistic relationship between DICER1 hotspot PVs and activation of the WNT signaling pathway in the formation of pulmonary tumors. These findings emphasize the importance of molecular testing in clinical practice such that detecting somatic DICER1 hotspot alterations aids in the diagnosis of rare lung cancers, which ultimately require special consideration with respect to disease severity and treatment.
Beyond transportation: Financial hardship, food insecurity, and care access barriers among US cancer survivors with transportation barriers to care.
Authors: Changchuan Jiang, Robin Yabroff, Lei Deng, Qian Wang, Stuthi Perimbeti, Ryan David Nipp, Xuesong Han
Journal: Journal of Clinical Oncology (2023)

6534 Background: Health care payers and providers increasingly focus on addressing social determinants of health (SDoH) in order to reduce disparities in care and patient outcomes in the US. Transportation barriers to health care, a key SDoH, are associated with increased emergency department use and mortality risk among cancer survivors. Transportation barriers may also be associated with other potentially addressable aspects of SDoH and access barriers. To inform future interventions, we examined financial hardship and barriers to timely care among cancer survivors with transportation challenges in a nationally representative sample. Methods: We identified 18,140 adults with a history of cancer from the 2011-2018 National Health Interview Survey. Transportation barriers were defined as delay in care due to lack of transportation over the past 12 months. Primary outcomes included 1) medical financial hardship (FH) in any of the three following domains: material (problems paying medical bills), psychological (worrying about medical bills), and behavioral hardship (delaying/forgoing care due to cost); 2) food insecurity (worrying food would run out); and 3) delayed care due to other factors (long wait times, inability to get an appointment quickly). We estimated the proportion of survivors who report any financial hardship, food insecurity, or other factors that lead to care delays and compared the age-sex adjusted prevalence of these barriers among cancer survivors by whether or not they reported transportation barriers using logistics regression. Results: Of the 18,123 cancer survivors, 2.9% reported having transportation barriers to care. Survivors with transportation barriers experienced significantly higher financial hardship, food insecurity, or other factors that lead to care delays than survivors without transportation barriers (86.0% vs 45.3%, p&lt;0.001). Additionally, survivors with transportation barriers were more likely to experience medical financial hardship (73.2% vs 38.3%, p&lt;0.001), including material (50.3% vs 27.1%, p&lt;0.001), behavior (57.5% vs 20.4%, p&lt;0.001), and psychological (33.5% vs 15.4%, p&lt;0.001) hardship than survivors without transportation barriers. Additionally, survivors with transportation barriers were more likely to experience food insecurity (43.9% vs 12.0%, p&lt;0.001) and care delays due to other factors (45.6% vs. 11.6%, p&lt;0.001). Conclusions: Most cancer survivors with transportation barriers to care also report struggling financially and experiencing additional barriers to timely care. Findings highlight the importance of screening and addressing social needs and comprehensive interventions to address barriers to care access in this vulnerable population.
Presentation of congenital soft-tissue sarcomas: A single institution experience.
Authors: Angela Parra Del Riego, Braden Olsen, Keishla Gonzalez, Camila Pabon, Gabriel Chamyan, Maggie Eidson Fader
Journal: Journal of Clinical Oncology (2023)

e23551 Background: Pediatric sarcomas make up 10% of pediatric tumors and involve a varied range of histological patterns with different prognosis which creates therapeutic challenges. Neonatal presentation is rare among sarcomas and poses further challenges in therapy. Methods: We present 5 cases of congenital sarcomas reporting pathology, genetics, treatment, and outcomes. We retrospectively identified 5 patients with sarcomas diagnosed in the neonatal period from a single institution in Miami from 2017 – 2022 in order to identify similarities between neonatal sarcomas. Our sarcomas included an embryonal rhabdomyosarcoma (RMS), infantile fibrosarcoma (IFS), rhabdoid tumor, and two undifferentiated sarcomas. Results: The presentation occurred between birth and four days old. Location at presentation was varied. Four of our patients were Nonrhabdomyosarcoma Soft Tissue Sarcomas (NRSTS). Only one patient was diagnosed prenatally, while three were diagnosed at birth, and one at 4 days of life. Three patients presented spindle cell pathology. One of our undifferentiated sarcomas was classified as IFS-like, Archer FusionPlex was negative for mutation. Our other undifferentiated sarcoma showed a COL1A1 gene rearrangement on chromosome 17q.21 with immunostains positive for BCOR, SMARCB1, SMARCA4. Congenital fibrosarcoma showed ETV6 fusion with NTRK and immunostains positive for FLI-1, SMA, CD34, INI-1. The RMS showed focal loss of PTCH1 and FANCC and had immunostains positive for desmin and myogenin. The metastatic rhabdoid tumor showed SMARCB1 whole gene deletion as well as a 570kB deletion in chromosome 22q11.23. Three patients were treated on ARST 0331 with vincristine, doxorubicin, and cyclophosphamide (VAC), with the undifferentiated sarcoma requiring advancement to ARST 0332. The patient with metastatic rhabdoid tumor was treated with AREN 0321. Four patients required surgery. We had 1-year-survival in three patients, all treated on ARST 0331 or ARST 0332. The patient with metastatic rhabdoid tumor died at 4 months of age while on AREN 0321, and our patient with IFS-like sarcoma decompensate and died at ten days old, prior to starting therapy. Conclusions: We show multiple genetic mutations with SMARCB1 alteration in both an undifferentiated sarcoma and a malignant rhabdoid tumor but otherwise found no significant pattern among individual sarcomas. Our cases show good outcomes for patients qualifying for ARST 0331. We highlight the need for improved methods of detection of pediatric tumors in utero.
A randomized controlled trial evaluating pretest cancer genetics educational video or in-person genetic counseling.
Authors: Yanin Chavarri Guerra, Andrea Morales Alfaro, Cesar Alcacio Vzquez, Araceli Carrillo Bedoya, Jazmin Arteaga, Jose Carlos Peñafort Zamora, Sofía Sánchez-Román, Daniela Ramirez Maza, Cynthia Villarreal-Garza, Nancy Reynoso, Alejandro Mohar, Juan Jose Calva Mercado
Journal: Journal of Clinical Oncology (2023)

10597 Background: Cancer genetic testing indications are rapidly expanding to determine treatment eligibility for patients with cancer, to identify individual cancer risk as well as to select family members at higher cancer risk when a pathogenic variant (PV) has been identified in the family. Currently, international guidelines recommend that all candidates for genetic testing should have genetic counseling to make an informed decision for genetic testing. However, with the increased demand for genetic testing, innovative ways to deliver pretest information are needed, especially in limited resource settings, where genetic cancer professionals’ availability is scarce. Methods: This is a non-inferiority trial comparing a pretest educational video to in-person genetic counseling. Participants referred for genetic cancer risk assessment at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were enrolled if they met international cancer genetic testing criteria and did not previously have genetic testing and/or counseling. The primary outcome was the uptake of genetic testing. Secondary outcomes included changes in genetic cancer knowledge, anxiety, and satisfaction using validated tools. Results: A total of 250 participants were included: 124 were randomized to the in-person genetic counseling arm and 126 to the educational video arm. Mean age was 47.9 years (SD 12.7), 86.4% were women, 37.2% had high-school or less and 86.4% had personal history of cancer (70% breast cancer). Overall, test acceptance was 100% in both arms. Cancer genetics knowledge improved in both groups: in-person from. 53 to .74 (diff .20; 95%CI .24-.26; p &lt; 0.05) and video from .51 to .68 (diff .16; 95%CI .20-.12; p &lt; 0.05). However, the in-person arm had a higher post counseling knowledge score (p 0.001). 43.5% and 42% of participants in the in-person and video arms had moderate-severe baseline anxiety. After intervention, both groups had a decrease in anxiety score: in-person from 5.2 to 4.7 (diff .58; 95% CI .09-1.08; p 0.01) and video from 4.9 to 4.1 (diff .75; 95%CI 0.42-1.08; p &lt; 0.05). Both groups were satisfied with genetic services (97.5% and 92.5%, respectively; p 0.34). Conclusions: A pretest educational video was non-inferior regarding genetic testing acceptance. It was also associated with improved genetic cancer knowledge and decreased anxiety levels. These results support the use of educational videos before genetic testing where in-person genetic counseling availability is limited. Clinical trial information: pending .
Disparities in minority patients with breast cancer under 40 years of age: A single center experience.
Authors: Rajvi Patel, Kimberly Ellison, Dawn Parsons, Nwabundo Ifeyinwa Anusim
Journal: Journal of Clinical Oncology (2023)

e18553 Background: Current guidelines recommend screening for breast cancer (BC) starting at age 40. However, BC in women under 40 years is increasing in incidence. Pathogenic germline mutations are found to be the driving force in nearly 17% of those diagnosed under 45 years and 50% of those under 30 years. Limited data is available on the prevalence of pathogenic mutations in minority patients. We conducted a retrospective analysis of young breast cancer patients from low socioeconomic backgrounds between 2010-2022 at a single center in Central Texas. Methods: Patients were selected based on a diagnosis of BC under 40 years old and living at or below 200% of federal poverty level as noted through their insurance status of Medicaid and Medical Assistance Program of Travis County. Data regarding age of diagnosis, demographics, clinical presentation, staging, germline mutations and outcomes were extracted from the medical record. Descriptive statistics were used to analyze the dataset. Results: A total of 125 patients were identified for the study. Median age of the cohort was 35 years old (range: 19-39 years). Demographics included 61 Hispanic patients (48.8%), 40 White patients (32.0%), 16 Black patients (12.8%) and &lt; 2% for each other group. Analysis of germline mutations was available for 86 patients. High risk mutations were identified in 28 patients, including 13 Caucasian women, 10 Hispanic women, and three Black women. BRCA mutations were the most common mutation (75%). Other mutations included CHEK2 (7.2%), MUTYH (7.2%), ATM (3.6%), PIK3CA (3.6%), PTEN (3.6%), RAD51C (3.6%) and RAD51D (3.6%). Variants of unknown significance were found in 18 patients, including 11 Hispanic women, four Black women and two White women. Forty patients had BC independent of mutations. Staging on initial diagnosis was available for 113 patients, 40.7% of which were locally advanced (28.3% in Stage III disease and 12.4% with metastatic disease). Advanced disease was higher in Hispanic patients (22/61) and Black patients (10/16) compared to White patients (10/40). Breast cancer subtypes included 22.8% with triple negative BC, 8.1% with HER2-enriched BC, 27.9% with hormone receptor (HR) positive and HER2 negative BC and 14.0% with both HR and HER2 positive BC. At the time of data review, only 30 patients were documented to have died, of which 22 died within five years of diagnosis. Five year death rate was 26.2% for Hispanic patients, 18.8% for Black patients and 7.5% for White patients in the study cohort. Conclusions: This study shows disparities among young Hispanic and Black patients with BC, particularly in the initial staging of BC and 5-year death rate. A large number of VUS were seen in minorities, suggesting little is known about the pathogenic nature of these mutations. Future prospective studies should consider investigating interplay between race and outcomes of those diagnosed with BC under 40 years old.
The impact of patient age on palliative care utilization and end-of-life outcomes among patients with metastatic breast cancer.
Authors: Carley Mitchell, Nickolas Stabellini, Zhengyi Chen, Pingfu Fu, Alberto J. Montero
Journal: Journal of Clinical Oncology (2023)

12034 Background: Among patients with advanced cancer, palliative care (PC) utilization is frequently associated with improved quality of life, less aggressive end of life (EOL) measures, and hospice enrollment at the time of death. While older age is often associated with less PC utilization. The interplay between patient age, site and timing of PC with resultant EOL trends is not well understood. We aimed to assess these variations within a single institution’s metastatic breast cancer (mBC) population. Methods: An IRB approved retrospective study was conducted. All adult, decedent, mBC patients from 2011-2022 were analyzed. Manual chart review extracted demographic and clinical data related to diagnosis, treatment, PC utilization and death. The relationship of patient age with PC utilization (including setting and timing), aggressive EOL measures, hospice care at the time of death, and hospice duration were evaluated. Univariate analyses were conducted and factors with a significance level p &lt; 0.15 were further evaluated on multivariable logistic regression. Results: 278 decedent mBC patients met inclusion criteria. Any form of PC interaction from date of metastatic diagnosis to date of death, and utilizing outpatient (OP) PC (i.e., only OP or OP + inpatient (IP)) during the last year of life were significantly associated with hospice enrollment at the time of death. Similarly, utilizing only OP PC (i.e., no IP) was significantly associated with a longer time on hospice care. There was a trend toward shorter hospice durations in mBC patients who received only IP PC, and patients who received any IP PC or had their first PC interaction &lt; 4 months prior to the time of death were more likely to experience ≥ 1 aggressive EOL measure. Young adults (&lt; 40) were significantly more likely to receive some form of PC throughout their disease course, with a trend toward receiving only IP PC. While no significant relationships were identified between age and EOL factors, there were trends toward young and middle-aged adults (40-64) receiving ≥ 1 aggressive EOL measure and less time on hospice compared to older adults (≥ 65). Conclusions: This study gives important insight into a breast cancer-specific female population. Results highlight the importance of PC, especially in the OP setting, and its effect on hospice enrollment prior to death. However, there appears to be an interesting dichotomy between young adults receiving more PC and worse EOL experiences compared to older adults receiving less PC and better EOL experiences. These results should guide and promote, early OP focused PC specifically for young and middle-aged adults to help improve challenging EOL transitions. [Table: see text]
Cardiac iron overload in pediatric oncology and bone marrow transplant survivors.
Authors: Rhea Hans, Celeste Cleveland, Sanjay Shah, Bethany Wisotzkey, Alexandra Maria Walsh
Journal: Journal of Clinical Oncology (2023)

e22022 Background: Cardiovascular late effects are a leading cause of mortality and morbidity in childhood cancer and Bone Marrow Transplant (BMT) survivors. In patients receiving chronic red blood cell transfusions, excess iron may be deposited in the liver, heart, and pituitary gland. Iron overload cardiomyopathy is characterized as a restrictive physiology with early diastolic dysfunction ultimately progressing to end-stage dilated cardiomyopathy. Iron loading in the heart can also lead to arrhythmias and increase myocardial ischemia reperfusion injury due to increased formation of reactive oxygen species. It is not yet known whether high transfused packed red blood cell (PRBC) volumes in cancer and BMT patients leads to cardiac iron deposition, and whether iron-induced cardiac injury contributes to the known cardiovascular late effects in these patients. Methods: 83 childhood cancer and BMT survivors with elevated serum ferritin levels and subsequent liver Magnetic Resonance (MR) imaging were identified. 18 patients (21.7%) who had liver iron content of &gt; 12mg/g (mean 16.0 ± 7.36 mg/g) also underwent Cardiac MRI (CMR) to determine cardiac iron content. Results: Median transfused blood volume was 393 ml/kg [95% Confidence Interval (CI) 170-780 ml/kg]. All 18 patients had at least one echocardiogram showing normal ventricular ejection fractions [mean 65.1 ± Standard Deviation (SD) 3.53%] and normal shortening fractions (mean 35.4 ± 3.67%). All patients had myocardial iron content within normal ranges (T2* relaxation time mean 35.1 msec ± 7.1 [normal &gt;20 msec], mean ± SD iron content 0.63± 0.2 mg/g dry weight, range 0.5-1.1). There was no association of cardiac iron content with transfused blood volume, anthracycline dose (mg/m 2 ) or liver iron content (Pearson Correlation Coefficients 0.27, 0.29 and 0.89 respectively). Conclusions: Childhood cancer and BMT patients receive multiple PRBC transfusions to treat symptomatic anemia. It is currently unknown whether excess iron deposition in the heart contributes to the cardiac effects of impaired diastolic function and ultimately systolic dysfunction. In this study, 11 of 18 patients (61.1%) with high levels of liver iron had at least 1 other risk factor for the development of future cardiac dysfunction (either anthracycline exposure, radiation to the chest or total body irradiation or both). Larger studies are needed to determine whether oncology patients with high levels of iron deposition in their liver are also at risk for clinically significant cardiac iron loading, and what risk factors may exist for elevated myocardial iron content.
Prevalence of cancer-related risk factors and associated cancer burden: A targeted literature review.
Authors: Abdul-Rahman Jazieh, Ashley Kim, Ze Cong, Whitney Jones
Journal: Journal of Clinical Oncology (2023)

e22525 Background: Cancer risk is impacted by a variety of factors besides age, which may lead to an elevated risk of cancer compared to the general population and have disparate impact on individuals. A targeted literature review was conducted to estimate the prevalence of, and the magnitude of risk of any cancer among, individuals with key risk factors, including chronic inflammation, immunodeficiency, genetics, recurrence, or behavioral. Methods: Data were abstracted using a structured search (2000-2022) in Embase, MEDLINE, and gray literature. The most recent/high quality publications involving adults with the specified risk factors were included (Table). For each risk factor, the prevalence and the standardized incidence ratio (SIR), which measures the heightened risk of cancer relative to the general population/individuals without the condition, were abstracted. Results: Overall, 35 studies were reviewed. Risk factors with the highest SIR of cancer included genetic predisposition (SIR=5.30-9.48 for Lynch syndrome or BRCA mutation), HIV (SIR=3.62), cirrhosis (SIR=2.00), and immunodeficiency disorders (SIR=1.99), with prevalence estimates of &lt;3.0% in the general population (Table). The most prevalent risk factors were tobacco use (42.8%; SIR=1.24), family history of cancer (35.6%; SIR=1.23), and obesity (34.8%; SIR=1.09). The prevalence tended to be higher for individuals aged 65+ (Table). Almost all studies reported an elevated risk of more than one type of cancer. Conclusions: Among individuals with known risk factors, an elevated risk of cancer was observed. Risk factors that confer the highest risk of cancer are mostly genetic and immune-related with low prevalence, while other risk factors with a moderately elevated risk of cancer are more prevalent. These estimates could be useful when determining which individuals need to be screened earlier and/or with comprehensive cancer screening options. [Table: see text]